ArticlePloS one2012
Upregulating Noxa by ER stress, celastrol exerts synergistic anti-cancer activity in combination with ABT-737 in human hepatocellular carcinoma cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Celastrol Enhanced Doxorubicin-Mediated Apoptosis in Saos-2 Osteosarcoma Cells.BioMed research international · 2026Article
- Nanoparticle-mediated celastrol ER targeting delivery amplify immunogenic cell death in melanoma.Journal of advanced research · 2025Article
- Endoplasmic Reticulum Stress and Cancer: Could Unfolded Protein Response Be a Druggable Target for Cancer Therapy?International journal of molecular sciences · 2023Review
- SHP2 inhibition improves celastrol-induced growth suppression of colorectal cancer.Frontiers in pharmacology · 2022Article
- Celastrol: An Update on Its Hepatoprotective Properties and the Linked Molecular Mechanisms.Frontiers in pharmacology · 2022Review
- HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.Journal of biomedical science · 2021Article
- Andrographolide Induces Noxa-Dependent Apoptosis by Transactivating ATF4 in Human Lung Adenocarcinoma Cells.Frontiers in pharmacology · 2021Article
- Article
- Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application.Frontiers in pharmacology · 2020Review
- Targeting the unfolded protein response in head and neck and oral cavity cancers.Experimental cell research · 2019Review
- Celastrol suppresses nitric oxide synthases and the angiogenesis pathway in colorectal cancer.Free radical research · 2019Article
- Celastrol inhibits colorectal cancer through TGF-β1/Smad signaling.OncoTargets and therapy · 2019Article
- Article
- A Mechanistic Overview of Triptolide and Celastrol, Natural Products fromFrontiers in pharmacology · 2018Review
- Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR.Oncotarget · 2017Article
- Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.Current genomics · 2017Review
- Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases.Frontiers in medicine · 2017Review
- PRIMA-1 targets the vulnerability of multiple myeloma of deregulated protein homeostasis through the perturbation of ER stress via p73 demethylation.Oncotarget · 2016Article
- Article
- The Natural Occurring Compounds Targeting Endoplasmic Reticulum Stress.Evidence-based complementary and alternative medicine : eCAM · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human hepatocellular carcinoma (HCC) represents biologically aggressive and chemo-resistant cancers. Owing to the low affinity with the apoptotic factor Mcl-1, the BH3 mimetic drug ABT-737 failed to exert potent cancer-killing activities in variety of cancer models including HCC. The current study demonstrated that combining ABT-737 and Celastrol synergistically suppressed HCC cell proliferation, and induced apoptosis which was accompanied with the activation of caspase cascade and release of cytochrome c from mitochondria. Further study revealed that the enhanced Noxa caused by Celastrol was the key factor for the synergy, since small interfering RNA-mediated knockdown of Noxa expression in HCC cells resulted in decreased apoptosis and attenuated anti-proliferative effects of the combination. In addition, our study unraveled that, upon Celastrol exposure, the activation of endoplasmic reticulum (ER) stress, specifically, the eIF2α-ATF4 pathway played indispensable roles in the activation of Noxa, which was validated by the observation that depletion of ATF4 significantly abrogated the Noxa elevation by Celastrol. Our findings highlight a novel signaling pathway through which Celastrol increase Noxa expression, and suggest the potential use of ATF4-mediated regulation of Noxa as a promising strategy to improve the anti-cancer activities of ABT-737.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.